Immunodeficiency associated with dedicator of cytokinesis-8 (DOCK8) deficiency represents a newly identified immunodeficiency disease characterized by a constellation of signs: severe cutaneous and sinopulmonary infections with bacterial organisms;severe cutaneous viral infections with Herpes simplex, Herpes zoster, Molluscum contagiosum, and Human Papilloma Virus; a marked elevation in serum IgE levels and eosinophilia; and decreased numbers of CD4 and CD8 T, and B-lymphocytes; homozygous or compound heterozygous mutations in the dedicator of cytokinesis 8 (DOCK8) gene. Patients with this syndrome die from bacterial sepsis, squamous cell carcinomas, or hematological malignancies. Hematopoietic stem cell transplantation (HSCT) represents a potentially life-saving treatment for immunodeficiency diseases due to stem cell defects. In this pilot study we propose to evaluate the efficacy and safety of allogeneic HSCT for DOCK8 deficiency. We are particularly interested in determining whether allogeneic HSCT reverses the lethal disease phenotype in DOCK8 deficiency by reconstituting normal host defense. The development of lethal squamous cell carcinomas and lymphomas arising from the immunodeficiency in DOCK8 deficiency supports therapeutic intervention before malignancy arises. Objectives To determine whether allogeneic HSCT reconstitutes T-lymphocyte and B-lymphocyte cell populations with normal donor cells at Day +100 and reverses the clinical phenotype of severe recurrent infections in patients with DOCK8 deficiency. To determine the safety of this allogeneic transplant regimen in DOCK8 deficiency by assessing transplant related toxicity, the incidence of acute and chronic graft-versus-host disease, immune reconstitution, overall survival, and disease-free survival Eligibility Patients 12-60 years old with DOCK8 deficiency who have suffered two or more life-threatening infections, and low CD4 and CD8 T-lymphocyte, and B-lymphocyte levels, or who have developed lymphoma or squamous cell carcinoma, and have either a 10/10 matched related donor or a 10/10 matched unrelated donor. Design DOCK8 deficiency patients with a matched related or unrelated donor will receive a pre-transplant conditioning regimen consisting of fludarabine 30 mg/m2/day on days -6, -5, -4, and -23, Busulfex 3.2 mg/kg/day on days -6, -5, -4, and -3, and HSCT on day 0. Post-transplant immunosuppression for graft-versus-host-disease (GVHD) prophylaxis will consist of methotrexate 5 mg/mg/day on days +1, +3, +6, and +11 and tacrolimus until day +180 if there is no evidence of graft-versus-host disease and patients have achieved full donor chimerism. Immunosuppression will be continued for up to one year or longer at the discretion of the PI.